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目的:探讨半胱氨酰天冬氨酸特异性蛋白酶(Caspase)-1抑制剂VX-765对急性胰腺炎的保护作用及其分子机制。方法:将60只SD大鼠(2019年8月购自河南省实验动物中心)按照随机数字表法分为假手术组、模型组和VX-765组，模型组和VX-765组经手术注射5%牛黄胆酸钠制备急性胰腺炎模型，对照组只进行手术不注射5%牛黄胆酸钠。建模24 h后对照组和模型组大鼠经腹腔注射生理盐水，VX-765组大鼠经腹腔注射50 mg/kg VX-765，治疗48 h后，观察3组大鼠存活率，采用自动生化仪检测血清淀粉酶活性；采用苏木精-伊红(HE)染色观察胰腺病理学变化；采用荧光定量聚合酶链反应(PCR)和酶联免疫吸附试验(ELISA)分析3组大鼠外周血白细胞介素(IL)-1β和IL-18 mRNA和蛋白表达水平，计量资料比较采用单因素方差分析。结果:VX-765组大鼠血清淀粉酶活性[(1 530.40±280.45) U/L]低于模型组血清淀粉酶活性[(2 910.43±429.12) U/L]，差异有统计学意义(n t＝4.891，n P<0.05)。VX-765组大鼠病理学评分(4.09±0.17)分低于模型组大鼠病理学评分(9.56±2.61)分，差异有统计学意义(n t＝3.018，n P<0.05)。VX-765组大鼠胰腺组织中IL-1β和IL-18 mRNA表达水平(1.96±0.14、1.47±0.17)低于模型组大鼠胰腺组织中IL-1β和IL-18 mRNA表达水平[(3.18±0.21)、(2.67±0.17)]，差异有统计学意义(n t＝2.999、2.104，n P<0.05)。VX-765组大鼠外周血清IL-1β和IL-18水平[(159.43±7.09)、(99.50±5.09) ng/L]低于模型组大鼠外周血清IL-1β和IL-18水平[(310.48±25.55)、(190.65±10.43) ng/L]，差异有统计学意义(n t＝2.801、2.466，n P<0.05)。n 结论:VX-765通过抑制Caspase-1活性，降低IL-1β和IL-18等炎性因子水平，进而缓解急性胰腺炎。“,”Objective:To investigate the protective effect of cysteinyl aspartate-specific protease (Caspase)-1 inhibitor VX-765 on acute pancreatitis and its molecular mechanism.Methods:A total of 60 Sprague Dawley (SD) rats purchased from Henan Experimental Animal Center from August 2019 to February 2020 were randomly divided into sham operation group, model group and VX-765 group according to the method of random number table. At 24 h after modeling, rats in sham operation group and model group were intraperitoneally injected with normal saline, and rats in VX-765 group were injected intraperitoneally with VX-756 (50 mg/kg). After 48 h of treatment, the survival rate of rats in the three groups was observed, and the serum amylase activity was detected by automatic biochemical analyzer. The pathological changes of pancreas were observed by hematoxylin and eosin (HE) staining. The peripheral blood interleukin (IL)-1β and IL-18 mRNA and proteins were analyzed by fluorescence quantitative polymerase chain reaction (PCR) and enzyme linked immunosorbent assay (ELISA). One-way ANOVA was used to compare the data between groups.Results:As compared with the model group [(2 910.43±429.12) U/L], the serum amylase activity [(1 530.40±280.45) U/L] in VX-765 group was significantly decreased (n t=4.891, n P<0.05). As compared with the model group (9.56±2.61), the pathological score of VX-765 group (4.09±0.17) was significantly decreased (n t=3.018, n P<0.05). As compared with the model group (3.18±0.21, 2.67±0.17), the expression levels of IL-1β and IL-18 mRNA in pancreatic tissue in VX-765 group (1.96±0.14, 1.47±0.17) were significantly reduced (n t=2.999, n P<0.05;n t=2.104, n P<0.05). As compared with the model group [(310.48±25.55), (190.65±10.43) ng/L], the levels of IL-1β and IL-18 in VX-765 group [(159.43±7.09), (99.50±5.09) ng/L] were significantly reduced in the model group (n t=2.801, n P<0.05;n t=2.466, n P<0.05).n Conclusion:VX-765 can alleviate acute pancreatitis by inhibiting Caspase-1 activity and reducing the levels of IL-1β and IL-18.